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Human Neural Stem Cells Overexpressing a Carboxylesterase Inhibit Bladder Tumor Growth
Sung S. Choi, Byung Hoon Chi, In Ho Chang, Kyung Do Kim
[ 2016³â 05¿ù 09ÀÏ 06½Ã 33ºÐ ]
Bladder cancer is a significant clinical and economic problem. Despite intravesical chemotherapy and immunotherapy, up to 80% of patients with non-muscle–invasive bladder cancer develop recurrent tumors, of which 20% to 30% evolve into more aggressive, potentially lethal tumors.

Recently, bladder cancer cells are considered to be mediators of resistance to current therapies and therefore represent strong candidates as biologic targets. No effective chemotherapy has yet been developed for advanced bladder cancer. It is desirable that a drug can be delivered directly and specifically to bladder cancer cells.

Stem cells have selective migration ability toward cancer cells, and therapeutic genes can be easily transduced into stem cells. In suicide gene therapy for cancer, stemcells carry a gene encoding a carboxylesterase (CE) enzyme that transforms an inert CPT-11 prodrug into a toxic SN-38 product, a topoisomerase 1 inhibitor. In immunodeficient mice, systemically transplanted HB1.F3.CE stem cells migrated toward the tumor implanted by the TCCSUP bladder cancer cell line, and in combination with CPT-11, the volume of tumors were significantly reduced. These findings may contribute to the development of a new selective chemothera-peutic strategy against bladder cancer.
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